Antigen recognition by T cells. Quantitative effects of augmentation by antibodies providing accessory interactions.
Although engagement of the TCR via antibody can be sufficient to trigger T cells, responses to Ag-bearing cells require additional "accessory" interactions in many cases. A method has been developed which allows preparation of surfaces bearing both purified class I alloantigen and coimmobilized antibodies. With this approach, it is possible to mimic such "accessory" interactions and to examine their quantitative effects on triggering via TCR-Ag interaction. Experiments are described which use this approach to examine triggering of degranulation by cloned, allogeneic CTL lines. Coimmobilization of antibodies specific for any of a variety of CTL surface proteins, including CD8, class I MHC proteins, CD45 (T200) and Thy-1, had the effect of decreasing the critical threshold density of Ag necessary to trigger responses, and decreasing by an order of magnitude the density required to stimulate a half-maximal response. Furthermore, in comparison with the 30-min lag seen with Ag alone, response was initiated immediately when an antibody specific for a CTL surface component was present. These results are consistent with the hypothesis that any CTL surface molecule having sufficient affinity for a component of the target surface can contribute to activation via the Ag-specific TCR; and at low Ag density could determine whether any response occurs.
Kane
K P
KP
Division of Membrane Biology, Medical Biology Institute, La Jolla, CA 92037.
Mescher
M F
MF
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D000950:Antigens, Ly / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D002448:Cell Adhesion; D004306:Dose-Response Relationship, Immunologic; D005089:Exocytosis; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D066298:In Vitro Techniques; D051379:Mice; D008961:Models, Structural; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000950:Antigens, Ly; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell